Radium-223 decreases PD-L1 expression in bone metastases: A study with [89Zr]Zr-atezolizumab PET and immunohistological correlation
9 affiliations
- 1Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands
- 2Department of Medical Oncology, Erasmus MC Cancer Institute, Doctor Molewaterplein 40 3015 GD, Rotterdam, the Netherlands
- 3Department of Medical BioSciences, Radboudumc, Nijmegen, the Netherlands
- 4Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands
- 5Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
- 6Department of Clinical Pharmacy and Pharmacology, UMC Groningen, University of Groningen, Groningen, the Netherlands
- 7Department of Internal Medicine, Franciscus Gasthuis and Vlietland Hospital, Rotterdam, the Netherlands
- 8Department of Medical Oncology, Radboud UMC, Nijmegen, the Netherlands
- 9Department of Medical Oncology, UMC Groningen, University of Groningen, Groningen, the Netherlands
Abstract
Purpose: Most patients with metastatic castration-resistant prostate cancer (mCRPC) do not benefit from treatment with immune checkpoint inhibitors targeting programmed cell death (ligand) 1 (PD-(L)1). Radiation might improve response to immunotherapy by increasing the immunogenicity of prostate cancer. The objective of this study was to investigate radium-223-mediated changes in the micro- and macroenvironment of mCRPC.
Methods: In this prospective, multicenter study (ICTRP NL-OMON26890), 28 patients with mCRPC and predominantly bone metastases were treated with radium-223, according to standard-of-care. Primary endpoint was failure-free survival (FFS). Imaging included sequential positron emission tomography (PET) with gallium-68 prostate-specific membrane antigen (68Ga-PSMA) and zirconium-89 atezolizumab (89Zr-atezolizumab) to quantify whole-body expression of PD-L1 in vivo (SUVmean/max). Paired PET analysis included nine patients. The immune status of patients was characterized in biopsies from bone metastases and in blood using (multiplex) immunohistochemistry (IHC) and flow cytometry, respectively. Sequential biopsy analysis included two patients.
Results: 89Zr-atezolizumab uptake in 68Ga-PSMA positive bone metastases showed high intra- and inter-patient heterogeneity. In the total volume of 68Ga-PSMA-positive bone lesions, the median SUVmean of 89Zr-atezolizumab was 2.5 (IQR 0.9–3.4) at baseline and 0.9 (IQR 0.5–2.5) after three cycles of radium-223, which was higher than the physiological uptake in bone marrow at baseline and after treatment with radium-223. After three cycles of radium-223, 89Zr-atezolizumab uptake decreased in bone metastases, independent of response on 68Ga-PSMA PET, and the number of lymphocytes in tumor tissue and blood decreased concomitantly.
Conclusions: Treatment of mCRPC bone metastases with radium-223 results in a significant decrease of in vivo PD-L1-expression on PET imaging and a decrease in immune cells in bone metastases and blood. These findings indicate that treatment with alpha emitting radium-223 alters the immune microenvironment, thereby potentially reducing the efficacy of PD-(L)1 inhibitors.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08175-9.
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BibTeX
@article{ling2026radium223,
title = {{Radium-223 decreases PD-L1 expression in bone metastases: A study with [89Zr]Zr-atezolizumab PET and immunohistological correlation}},
author = {Sui Wai Ling and Anouk de Jong and Mark Gorris and Marcel Segbers and Laura Graven and Marjolein van Driel and Geert van Leenders and Khrystany Isebia and Marjolijn Lub – de Hooge and Paul Hamberg and Niven Mehra and Mandy van Brakel and Ronald de Wit and Reno Debets and Elisabeth de Vries and Tessa Brabander and Jolanda de Vries and Astrid van der Veldt},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
year = {2026},
month = sep,
doi = {10.1007/s00259-026-08175-9},
url = {https://doi.org/10.1007/s00259-026-08175-9},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Radium-223 decreases PD-L1 expression in bone metastases: A study with [89Zr]Zr-atezolizumab PET and immunohistological correlation
AU - Sui Wai Ling
AU - Anouk de Jong
AU - Mark Gorris
AU - Marcel Segbers
AU - Laura Graven
AU - Marjolein van Driel
AU - Geert van Leenders
AU - Khrystany Isebia
AU - Marjolijn Lub – de Hooge
AU - Paul Hamberg
AU - Niven Mehra
AU - Mandy van Brakel
AU - Ronald de Wit
AU - Reno Debets
AU - Elisabeth de Vries
AU - Tessa Brabander
AU - Jolanda de Vries
AU - Astrid van der Veldt
PY - 2026
DA - 2026/09/12
JO - European Journal of Nuclear Medicine and Molecular Imaging
DO - 10.1007/s00259-026-08175-9
UR - https://doi.org/10.1007/s00259-026-08175-9
AB - Purpose: Most patients with metastatic castration-resistant prostate cancer (mCRPC) do not benefit from treatment with immune checkpoint inhibitors targeting programmed cell death (ligand) 1 (PD-(L)1). Radiation might improve response to immunotherapy by increasing the immunogenicity of prostate cancer. The objective of this study was to investigate radium-223-mediated changes in the micro- and macroenvironment of mCRPC. Methods: In this prospective, multicenter study (ICTRP NL-OMON26890), 28 patients with mCRPC and predominantly bone metastases were treated with radium-223, according to standard-of-care. Primary endpoint was failure-free survival (FFS). Imaging included sequential positron emission tomography (PET) with gallium-68 prostate-specific membrane antigen (68Ga-PSMA) and zirconium-89 atezolizumab (89Zr-atezolizumab) to quantify whole-body expression of PD-L1 in vivo (SUVmean/max). Paired PET analysis included nine patients. The immune status of patients was characterized in biopsies from bone metastases and in blood using (multiplex) immunohistochemistry (IHC) and flow cytometry, respectively. Sequential biopsy analysis included two patients. Results: 89Zr-atezolizumab uptake in 68Ga-PSMA positive bone metastases showed high intra- and inter-patient heterogeneity. In the total volume of 68Ga-PSMA-positive bone lesions, the median SUVmean of 89Zr-atezolizumab was 2.5 (IQR 0.9–3.4) at baseline and 0.9 (IQR 0.5–2.5) after three cycles of radium-223, which was higher than the physiological uptake in bone marrow at baseline and after treatment with radium-223. After three cycles of radium-223, 89Zr-atezolizumab uptake decreased in bone metastases, independent of response on 68Ga-PSMA PET, and the number of lymphocytes in tumor tissue and blood decreased concomitantly. Conclusions: Treatment of mCRPC bone metastases with radium-223 results in a significant decrease of in vivo PD-L1-expression on PET imaging and a decrease in immune cells in bone metastases and blood. These findings indicate that treatment with alpha emitting radium-223 alters the immune microenvironment, thereby potentially reducing the efficacy of PD-(L)1 inhibitors. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08175-9.
SN - 1619-7070
SN - 1619-7089
ER -